The Important Role of Interleukin-2 in COVID-19

Abstract

There is controversial literature about the effects of the interleukin-2 (IL-2) cytokine family in COVID-19 pathogenesis and immunity. So we aimed to identify the potential in the role of the IL-2 family in COVID-19. A narrative review search was done through online databases, including PubMed, Scopus, and Web of Science. The search deadline was up to December 2022. We applied no time limits for the searching strategy. After retrieving articles from the databases, the authors summarized the data into two data extraction tables. The first data extraction table described the changes in the IL-2 cytokine family in COVID-19 and the second table described the therapeutic interventions targeting IL-2 family cytokines. The results of the literature on the role of the IL-2 cytokine family do not show a singular rule. IL-2 cytokine family can change during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some studies suggest that IL-2 cytokine family rise during the infection and cause severe inflammatory response and cytokine storm. These cytokines are shown to be increased in immunocompromised patients and worsen their prognosis. In individuals without underlying disease, the upregulation of the IL-2 family shows the clinical outcome of the disease and rises with disease severity. However, some other studies show that these cytokines do not significantly change. IL-2 cytokine family is mostly upregulated in healthy individuals who had vaccination, but immunocompromised patients did not show significant changes after a single dose of vaccines, which shows that these patients need booster doses for efficient immunity. IL-2 cytokine family can also be used as immunotherapy agents in COVID-19.

Clinical and immunological comparison of COVID-19 disease between critical and non-critical courses: a systematic review and meta-analysis

“…However, IL-2 levels were increased in non-critical patients but decreased in critical ones. When present in low concentrations, IL-2 can prevent CD4+ T and CD8+ T-cell activation by maintaining T regulatory cell activity and survival ( 36 ). As a result, this could lead to a significant drop in CD8+ T-cells and lymphocytes in COVID-19 critical patients ( 37 ).…”

Immunogenicity Assessment of the SARS-CoV-2 Protein Subunit Recombinant Vaccine (CoV2-IB 0322) in a Substudy of a Phase 3 Trial in Indonesia

“…CD4+ cells are the primary source of IL-2 production, as well as CD8+ cells to a lesser extent. By evaluating both cytokine production capacities, we explored the vaccines' efficacy in activating T-cells, promoting a Th1-biased response, and generating memory cells contributing to long-term protection against SARS-CoV-2 infection [31][32][33].…”

Alteration of circulating ACE2-network related microRNAs in patients with COVID-19

“…We identified the following top targeted pathways affected by analyzed miRNAs: IL-2 signalling pathways, signaling events mediated by T cell protein tyrosine phosphatase (TC-PTP) and HIF-1 transcriptional activity in hypoxia which would require further investigation. Regarding IL-2, certain studies propose that there is an elevation in the IL-2 cytokine family levels during the infection, leading to a heightened inflammatory response and the potential occurrence of a cytokine storm 44 . Elevated cytokine levels worsen prognosis in immunocompromised patients, while in those without underlying conditions, IL-2 family upregulation correlates with disease severity.…”