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The kinetics of inhibitory immune checkpoints during and post-COVID-19: the knowns and unknowns

Journal

CLINICAL AND EXPERIMENTAL MEDICINE
Volume 23, Issue 7, Pages 3299-3319

Publisher

SPRINGER-VERLAG ITALIA SRL
DOI: 10.1007/s10238-023-01188-w

Keywords

Inhibitory immune checkpoint; COVID-19; Kinetics; Complications; Prognosis

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The immune system is regulated by inhibitory immune checkpoints to prevent excessive immune responses, but chronic infections can result in sustained expression of these checkpoints, leading to reduced immune cell functioning and more severe disease complications. Pathogens can also exploit these immune checkpoints to evade immune mechanisms.
The immune system is tightly regulated to prevent immune reactions to self-antigens and to avoid excessive immune responses during and after challenges from non-self-antigens. Inhibitory immune checkpoints (IICPs), as the major regulators of immune system responses, are extremely important for maintaining the homeostasis of cells and tissues. However, the high and sustained co-expression of IICPs in chronic infections, under persistent antigenic stimulations, results in reduced immune cell functioning and more severe and prolonged disease complications. Furthermore, IICPs-mediated interactions can be hijacked by pathogens in order to evade immune induction or effector mechanisms. Therefore, IICPs can be potential targets for the prognosis and treatment of chronic infectious diseases. This is especially the case with regards to the most challenging infectious disease of recent times, coronavirus disease-2019 (COVID-19), whose long-term complications can persist long after recovery. This article reviews the current knowledge about the kinetics and functioning of the IICPs during and post-COVID-19.

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