Regulatory T Cells in Immunopathogenesis and Severity of COVID-19: A Systematic Review

Abstract

Background: Severe cases of coronavirus disease 2019 (COVID-19) often experience hyper-inflammatory reactions, acute respiratory distress syndrome (ARDS), blood clotting, and organ damage. The most prominent immunopathology of advanced COVID-19 is cytokine release syndrome, or "cytokine storm" which is attributed to a defect of immune-regulating mechanisms. This study aimed to evaluate the role of regulatory T cells (Tregs) as one of the main cells that maintain immune homeostasis. Methods: A systematic search was performed on PubMed, Scopus and Google Scholar. All English articles related to Treg’s role in COVID-19 were extracted and evaluated by two researchers independently. Study eligibility was assessed based on modified Evidence-based librarianship (EBL) checklist. Results: Nineteen eligible studies comparing Treg cells in COVID-19 patients with the control group or comparing alterations of this cell in severe and moderate patients were evaluated. Currently, there is no consensus regarding the increase or decrease of Tregs in COVID-19 patients compared to the control group. However, it was observed that Tregs in severe COVID-19 patients were significantly lower than moderate patients, resulting in uncontrolled inflammation and cytokine storm. Conclusion: Regulatory T cells can be one of the determinants of disease severity and prognosis in patients with COVID-19 by inhibiting rampant inflammation and preventing cytokine storms.

Immune responses in mildly versus critically ill COVID-19 patients

“…Current evidence indicates smaller amounts of Treg cells in correlation with disease severity in the peripheral blood of COVID-19 patients ( 115 , 157 , 158 ). The frequency of this subset increases during the recovery phase of the disease ( 159 ).…”

Celastrol alleviates murine lupus nephritis via inducting CD4+Foxp3+ regulatory T cells

“…Tregs are a small subgroup of T cells that are indispensable to immune tolerance and immune homeostasis [44]. Deficiencies in the function or number of Tregs result in graft rejection and diverse autoimmune disorders, including rheumatoid arthritis, graft-versus-host disease and SLE [45].…”

A scoping review of regulatory T cell dynamics in convalescent COVID-19 patients – indications for their potential involvement in the development of Long COVID?

“…Studying COVID-19, previous reviews have already made an effort to characterize Tregs during the acute phase of a SARS-CoV-2-infection ( 38 – 41 ). Although evidence exists that alterations in the Treg compartment might contribute to the immunopathology of COVID-19, the literature concerning their functionality and frequency during the acute illness is controversial.…”