ABSTRACT
Background: Severe COVID-19 is less common in children than in adults. Increasing evidence show that distinct immune-pathological changes can persist weeks or months after SARS-CoV2 infection, leading to Long COVID (LC). We investigated the systemic type I/III interferon (IFN-I/III) and inflammation response in peripheral blood mononuclear cells (PBMCs) of children with and without LC symptoms. Method(s): Blood samples were collected from children attending Umberto I hospital of Rome, within 3-6 months after a SARS-CoV-2 positive test and from control children. RNA was extracted from PBMCs for determining the levels of IFN-I (IFN-Alpha2, -Beta, -Epsilon and -Omega), IFN-III (IFN-Lambda1-3), NLRP3 and IL-1beta genes, and miR-141 expression by quantitative RealTime-PCR assays, normalized to housekeeping GUS gene and RNU6B, respectively. Result(s): 28 participants (M 12.5y SD 3.0) with LC symptoms, 28 participants (M 11.8y SD 3.0) without LC symptoms and 18 children who've never had SARS-CoV- 2 infection (M 10.5y SD 3.1) were enrolled. Comparing the three study groups, we found reduced levels of IFN-Lambda1, IFN-Lambda2 and IFN-Lambda3 (p=0.006, p< 0.001, p=0.012, respectively;Kruskal-Wallis (KW) test) mRNA in patients who have had SARS-CoV-2 infection as opposed to control group, whereas transcript levels of IFN-Epsilon (p= 0.019;KW test) were increased in the former with respect to the latter group;as well, remaining IFN-I genes analyzed showed a tendency to be up-regulated. As far as NLRP3 and IL-1beta levels was concerned, these genes were increased in LC patients (p< 0.001 for both genes;KW test). Additionally, miR-141, which has been reported to regulate inflammasome response, was overexpressed in LC patients (p< 0.001;Mann-Whitney test). Conclusion(s): These results showed a decreased levels of IFN-III mRNAs and an overexpression of IFN-Epsilon in children after 3-6 months of SARS-CoV-2 infection regardless of development of LC symptoms, suggesting that SARSCoV- 2 could have caused dysregulation of IFN response through unknown mechanisms (e.g. epigenetic modifications). Also, we found an overexpression of miR-141, NLRP3 and IL-1beta mRNAs in LC patients, indicating that a prolonged activation of inflammasome pathways could be associated with the development of LC symptoms.