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11 April 2024 : Clinical Research  

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

Kacper Toczyłowski ORCID logo1ACDEFG, Dawid Lewandowski1AB, Diana Martonik ORCID logo2BE, Anna Moniuszko-Malinowska ORCID logo3ABE, Ewelina Kruszewska ORCID logo3BE, Anna Parfieniuk-Kowerda ORCID logo2BE, Robert Flisiak ORCID logo2BE, Artur Sulik ORCID logo1ABDE

DOI: 10.12659/MSM.944052

Med Sci Monit In Press; DOI: 10.12659/MSM.944052  

Available online: 2024-04-11, In Press, Corrected Proof

Publication in the "In-Press" formula aims at speeding up the public availability of the pending manuscript while waiting for the final publication. The assigned DOI number is active and citable. The availability of the article in the Medline, PubMed and PMC databases as well as Web of Science will be obtained after the final publication according to the journal schedule


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.
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-α, 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.
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-α, 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.
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.

Keywords: Anti-Inflammatory Agents; COVID-19; Matrix Metalloproteinases; Tissue Inhibitor of Metalloproteinases; COVID-19 Serotherapy; Tocilizumab


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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750