Long COVID: Further Advances in Our Understanding of the Role of Specific Chemokines (CCR5, CCR6, CCR9, and CCL3) in Pediatrics

Authors
Hamidreza Farhadirad
Nasir Arefinia
Zohreh-Al-Sadat Ghoreshi
Fateme Sadeghzade
10.61186/ibj.25th-11th-IACRTIMSS
Abstract
Introduction: ARS-CoV-2 infection (COVID-19) is a major pandemic that has caused significant mortality and morbidity worldwide. About 80% of patients had mild or moderate disease, and 5% of patients with severe disease developed severe disease. Long COVID-19, also known as post-COVID-19 syndrome, is a condition in which individuals continue to experience symptoms for weeks or months after recovering from COVID-19. There is a lack of sufficient data on the risk factors for post-COVID-19 sequelae in children. This study aimed to evaluate the long-term effects of severe COVID-19 on promotor methylation and expression genes, including CCR5, CCR6, CCR9, and CCL3 in children.

Methods and Materials: Clinical data and blood samples from 94 long COVID patients and 25 healthy subjects were collected. Promotor methylation and mRNA expression of CCR5, CCR6, CCR9, and CCL3 genes in these patients and control group were assessed through methylation-specific PCR and real-time PCR assay.

Results: Our result indicated that promotors of CCR5 (p = 0.01) and CCL3 (p = 0.006) in convalescence COVID-19 children were hyper-methylated compared to the healthy control group. Subsequently, CCR5 and CCL3 transcripts decreased compared to the control group (p = 0.01). In addition, CCL3 transcript in children with convalescent COVID-19 decreased compared to the control group (p = 0.008). However, we did not observe any significant modification in the transcript levels of CCR6 (p = 0.7) and CCR9 (p = 0.46) in children with convalescent COVID-19 compared to all the control groups.

Conclusion and Discussion: The CCR5 and CCL3 promoter region DNA methylation and the subsequent decrease in the expression of these genes were possibly correlated with long-term COVID-19 occurrence in children. Our study revealed additional data on the SARS-CoV-2-mediated inflammatory response.



Keywords
CCR5 receptor antagonists
Chemokine CCL3
Methylation