Background
Myocardial injuries have been observed after COVID-19 in previously healthy children, regardless of COVID-19 severity. Immune dysregulation may play a role in post-COVID cardiac alterations but remains unexplored in children. This study evaluated the immune response in children with or without asymptomatic cardiac contractility alterations after mild SARS-CoV-2 infection.
Methods
A prospective, observational study was conducted at the University of Padua (Italy) from May-September 2020 on children aged 0-<18 years after mild COVID-19. Three months post-COVID-19, speckle-tracking echocardiography assessed cardiac function, and blood samples were collected for immunological analysis. Children with cardiac contractility alterations (C-ACC) were defined by a regional peak systolic strain <-16% in at least two segments. Immune activated and regulatory T (Tregs) cells were analyzed via flow cytometry, while neutralizing antibody (NAb) titers were assessed via the Plaque Reduction Neutralization Test (PRNT). Geometric mean titers (GMTs), 95% confidence intervals (95%CI), medians, and interquartile ranges (IQRs) were compared between C-ACC and children without cardiac contractility alterations (C-NACC). Spearman correlation was assessed between immune activation, Tregs, and NAbs.
Results
Sixty-seven children were studied (mean age: 7±4.8 years; male/female: 28/39), including 16 C-ACC and 51 C-NACC. All C-ACC children had asymptomatic cardiac contractility alterations with normal left ventricular ejection fraction. No differences in systemic symptoms were found between C-ACC and C-NACC (11/16 [68.8%] vs 31/51 [60.8%]; p=ns). Notably, C-ACC exhibited lower Treg frequencies (3.17 [IQR: 1.26-5.6] vs 6.96 [IQR: 3.55-11.57]) and shorter telomeres (4.82 [IQR: 3.57-5.81] vs 6.28 [IQR: 4.03-7.69]) compared to C-NACC. At similar activated CD8 cell frequencies between the two groups, an inverse correlation between Tregs and activated CD8 cells was observed in C-NACC (r=-0.476) (Figure). NAb titers were higher in C-NACC than in C-ACC (4.61 [95% CI: 4.17-5.10] vs 3.85 [95% CI: 3.10-4.77]), with a positive correlation observed between NAb titers and Tregs in C-NACC (r= 0.709).
Conclusions
Higher frequencies of Tregs contributed to reduced T cell activation, resulting in a more specific response to SARS-CoV-2 in C-NACC. Conversely, prior immune activation led to significant cell replication, as evidenced by greater telomere shortening, which may have contributed to cardiac contractility alterations in C-ACC.