The Role of Immune Regulatory Molecules in COVID-19

As the fifth pandemic in the 21st century, coronavirus 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the most prominent global concern in the last 2 years. Variable manifestations characterize SARS-CoV-2 infection. Despite the design and production of effective vaccines and their considerable effect on reducing the COVID-19 prevalence and mortality rate, no definitive cure for the disease has yet been found. Mutations may also affect the effectiveness of vaccines. The host immune response to the pathogen has a critical role in the course of the disease. Positive and negative signals often balance the immune system. Immune regulatory molecules, also known as immune checkpoint receptors, balance the immune responses. These molecules mainly have inhibitory functions and prevent hyperactivation of immune cells or trigger adverse signaling pathways. For a decade, the immune checkpoint blockade, as a therapeutic target for cancer immunotherapy, has been utilized. Some of the inhibitory receptors are recognized as exhaustion markers on T cells. The signaling pathway of these markers restricts the function of T cells against viral infection. Dysregulation of T cells was observed in SARS-CoV-2 infection and can modify proliferation, differentiation, cytokine production, and type of response. The pivotal role of immune inhibitory receptors in the function of acquired, cell-mediated, immune defense T cells makes them a fascinating subject to study. This review article summarized recent findings on immune regulatory molecules and their role in SARS-CoV-2 infection, hoping to find a way to design novel treatments.