Frequency of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in peripheral blood of pediatric patients with SARS CoV-2 Infection: a pilot study

Background: Cytokine storm has been observed in some patients with SARS-CoV-2 due to excessive pro-inflammatory response. Foxp3(+) regulatory T cells (Tregs) are a distinct population of CD4(+) lymphocytes identified by their expression of transcription factor forkhead homeobox protein-3 (Foxp3). These cells down-regulate immune responses in inflammatory and autoimmune diseases. Objective: This pilot study was aimed to investigate the levels of CD4(+)CD25(+)Foxp3(+) Tregs in children with SARS-CoV-2. Methods: frequency of Tregs was measured by flow cytometry in 20 patients with SARS-CoV-2, 6 months to 15 years old;6 had COVID-19 and 14 had multisystem inflammatory syndrome in children (MIS-C). They were compared to 20 age-and sex-matched healthy children as a control group. Results: There was no significant difference between patients with SARS-CoV-2 infection and healthy control children in the frequency of Tregs (P=0.068). Decreased numbers of Tregs was found in only 10% of SARS-CoV-2 patients. Patients with severe SARS-CoV-2 were comparable to those with moderate disease in terms of Tregs' levels. The frequency of Tregs correlated negatively with neutrophil counts in our series (p=0.036). Attempts of correlation with other inflammatory markers of SARS-CoV-2 were insignificant. Conclusion: Decreased levels of Tregs were found in only 10% of our SARS-CoV-2 infected children. The frequency did not correlate with the disease severity or levels of routine inflammatory markers of SARS-CoV-2. Thus, Tregs expression does not seem to have a role in the up-regulated immune response seen in moderate and severe SARS-CoV-2 infection. Our conclusions are limited by the sample size.