The role of regulatory T cells in COVID-19

In COVID-19, Treg cells may significantly influence disease severity, yet the precise mechanisms through which Tregs impact the disease course remain elusive. Moreover, our understanding of how these cells affect immunity induced by SARS-CoV-2 vaccines is limited. SpiNTec, a chimeric vaccine, has demonstrated efficacy in stimulating a protective immune response mediated by CD4+ and CD8+ T cells, resulting in notable reductions in viral load and COVID-19 pathology in animal models and ongoing phase I/II clinical trials. Consequently, this study aims to elucidate the role of Tregs in COVID-19 within the contexts of both disease progression and vaccine-induced immunity. Preliminary findings indicate that SpiNTec decreases the frequency of Tregs in the lung, suggesting a potential mechanism of action. The investigation will involve analyzing regulatory T cells during the acute phase of infection by infecting K18-hACE2 mice with the SARS-CoV-2 Omicron strain and assessing samples at 5 and 10 days post-infection. Additionally, the long COVID model will be validated in mice infected with varying doses of SARS-CoV-2, followed by sample collection at 30, 45 and 90 days post-infection. Furthermore, the study will analyze regulatory T cells in patients with long COVID by isolating PBMCs and employing flow cytometry techniques. This study aims to enhance understanding of the role of Tregs in the immunopathology of COVID-19 and vaccine efficacy, contributing to the development of new therapeutic strategies and vaccine development.This study was previously approved by the Research Ethics Committee of the Hospital das Clínicas of Ribeirão Preto (Approval Number: 6.470.180) and also by the Animal Use Ethics Committee (No. 1152/2022) of the Ribeirão Preto Medical School - USP.