IL-7 in SARS-CoV-2 Infection and as a Potential Vaccine Adjuvant

Abstract

IL-7/IL-7R signaling is critical for development, maturation, maintenance and survival of many lymphocytes in the thymus and periphery. IL-7 has been used as immunotherapy in pre-clinical and clinical studies to treat cancer, HIV infection and sepsis. Here, we discuss the critical function of IL-7 in diagnosis, prognosis and treatment of COVID-19 patients. We also summarize a promising role of IL-7 as a vaccine adjuvant. It could potentially enhance the immune responses to vaccines especially against SARS-CoV-2 or other new vaccines.

Keywords: COVID-19; IL-7; IL-7R; SARS-CoV-2; adjuvant.

Figure 1

IL-7/IL-7R signaling and clinical applications. IL-7 is mainly produced by stromal cells, epithelial cells, keratinocytes, dendritic cells, follicular dendritic cells and hepatocytes; and consumed by IL-7R expressing cells for development, proliferation, survival and maintenance (1). Preclinical and clinical studies showed that HIV-infected (2), cancer (3), sepsis (4) and COVID-19 (–7) patients benefited from IL-7 treatment.

Figure 2

IL-7 during SARS-CoV-2 infection. (A) Under homeostatic conditions, there is a balance between IL-7 and IL-7R; IL-7 is important for development of T cells in the thymus and survival of T cells in the periphery. (B) Decreased consumption of IL-7 and downgraded expression of IL-7R associated with elevated plasma/serum levels of IL-7 in SARS-CoV-2 infection. IL-7 downregulates its own receptor, IL-7R. Furthermore, antiviral activity and survival of T cells will be decreased due to imbalance of IL-7/IL-7R, leading to lymphopenia. The lymphopenia in turn leads to decreased consumption of IL-7 because T cells are the main consumers of IL-7. This in turn leads to higher circulating levels of IL-7, in a feedback loop.