Differential Inflammatory Responses in Adult and Pediatric COVID-19 Patients: Implications for Long-Term Consequences and Anti-Inflammatory Treatment

BACKGROUND COVID-19 manifests with varying degrees of severity across different age groups; adults typically experience more severe symptoms than children. Matrix metalloproteinases (MMPs), known for their role in tissue remodeling and immune responses, may contribute to the pathophysiological disparities observed between these groups. We sought to delineate differences in serum MMP profiles between adult and pediatric COVID-19 patients, assess the influence of anti-inflammatory treatment on MMP levels, and examine potential implications for long-term consequences. MATERIAL AND METHODS Serum samples from adult and pediatric COVID-19 patients, alongside controls, were analyzed for MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-12, MMP-13, EMMPRIN, TNF-alpha, TIMP-1, TIMP-2, TIMP-3, and TIMP-4. A subset of adult patients received treatment with glucocorticoids, tocilizumab, and convalescent plasma, and MMP levels were compared with those of untreated patients. RESULTS Elevated levels of MMP-1, MMP-7, TIMP-1, and TIMP-2 were observed in adult and pediatric patients. Adult patients displayed higher concentrations of MMP-3, MMP-8, MMP-9, TNF-alpha, and TIMP-4 than children. Post-treatment reduction in MMP-1, MMP-8, MMP-9 levels was observed, with median decreases from 21% to 70%. MMP-3 and MMP-7 remained largely unchanged, and MMP-2 concentrations increased after treatment. Notably, anti-inflammatory treatment correlated with reduced post-treatment MMP levels, suggesting potential therapeutic benefit. CONCLUSIONS Distinctive inflammatory responses in COVID-19 were evident between adults and children. While certain MMPs exhibited post-treatment reduction, the persistence of elevated levels raises concerns about potential long-term consequences, including lung fibrosis. Our findings emphasize the need for personalized treatment strategies and further investigation into the dynamics of MMP regulation in COVID-19.