D1.423 - Immunological mechanisms underlying pulmonary manifestations in pediatric long COVID patients

Pediatric long COVID involves symptoms persisting over 12 weeks following acute SARS-CoV-2 infection, potentially driven by viral persistence, immune dysregulation, or endothelial dysfunction. Around 4-25% of infected children experience symptoms lasting at least three months, with one-third reporting respiratory issues. A previous epidemiological study at National Taiwan University Children’s Hospital following 879 pediatric long COVID patients revealed that 33% presented with a persistent cough, 20% with fatigue, 15% with dyspnea, and 5% with chest pain. In this study, we aimed to further investigate the immunological profiles of the children with long COVID.

We divided the subjects into three groups: a long COVID group (LC, n=42) with persistent pulmonary symptoms like cough or dyspnea; a convalescent control group (CC, n=65) without pulmonary symptoms; and a healthy, uninfected control group (HC, n=56). We also recorded patient characteristics, evaluated lung function using spirometry, measured serum antibodies, cytokines, and chemokines via ELISA/multiplex assays, and analyzed lymphocyte subsets using flow cytometry.

Lung function tests showed the LC group had significantly lower FEV1 (77.2%) and FVC (79.3%) predicted percentages compared to controls (p < 0.001). Immunological analysis of the LC group indicated heightened inflammation, characterized by elevated Th2 cytokines (IL-10) and increased Th2 chemokines (TARC, CCL2, CCL11, CCL19). Furthermore, there was a noticeable decrease in regulatory T cells (Treg) and increase in memory T cells. Notably, during a two-year follow-up, these differences in Treg and Memory CD4 T cells fully resolved.

Based on the study, long COVID with pulmonary symptoms is correlated with increased inflammation. This condition is mechanistically characterized by a decrease in regulatory T cells (Treg) and a simultaneous increase in memory T cells. Furthermore, the immune profile features an upregulation of Th2 cytokines, specifically IL-10, as well as elevated Th2 chemokines including TARC, CCL2, CCL11, and CCL19. Importantly, this represents a transient immune dysregulation, as a two-year follow-up showed no continuing differences in Treg or memory T cells. We believe that the results here might help us in further elucidating the mechanisms involved in long COVID.