SARS-CoV-2 infection: The role of PD-1/PD-L1 and CTLA-4 axis

The outbreak of SARS-CoV-2 in Wuhan of China in December 2019 and its worldwide spread has turned into the COVID-19 pandemic. Respiratory disorders, lymphopenia, cytokine cascades, and the immune responses provoked by this virus play a major and fundamental role in the severity of the symptoms and the immunogenicity which it causes. Owing to the decrease in the inflammatory responses' regulation in the immune system and the sudden increase in the secretion of cytokines, it seems that an investigation of inhibitory immune checkpoints can influence theories regarding this disease's treatment methods. Acquired cell-mediated immune defense's T-cells have a key major contribution in clearing viral infections thus reducing the severity of COVID-19's symptoms. The most important diagnostic feature in individuals with COVID-19 is lymphocyte depletion, most importantly, T-cells. Due to the induction of interferon-γ (INF-γ) production by neutrophils and monocytes, which are abundantly present in the peripheral blood of the individuals with COVID-19, the expression of inhibitory immune checkpoints including, PD-1 (programmed death), PD-L1 and CTLA4 on the T-cells' surface is enhanced. The purpose of this review is to discuss the functions of these checkpoints and their effects on the dysfunction and exhaustion of T-cells, making them almost ineffective in individuals with COVID-19, especially in the cases with extreme symptoms.