The decline in circulating lymphocyte number in COVID-19 patients can also attribute to the ‘exhausted’ state of these cells (Chen and John Wherry, 2020). The heightened viral load and presence of specific inhibitory signals bring about changes in the transcriptional and effector profile of T cells in a coordinated manner. Initially, they lose their property to secrete effector cytokines and gradually proceed to reduced expression of essential maintenance and activation surface receptors (Wherry and Kurachi, 2015). A subsequent increase in the expression of inhibitory receptors and associated morphological changes result in the elimination of these cells from the circulation (Wherry and Kurachi, 2015). CD4+ T cell exhaustion determines their insufficient secretion of effector molecules like IL-2, IL-10, IL-21, IFN-γ and TNF-α with a concomitant increase in inhibitory molecular signaling by PD-1, CTLA-4, LAG-3, CD244 (2B4), and TIM-3 (Blank et al., 2019; Dong et al., 2019). Similarly, CD8+ T cell exhaustion is determined by reduced expression of IL-2, IFN-γ, TNF-α, and cytolytic granules. Besides, decreased expression of T cell maintenance receptors CD122 and CD127, and increase in inhibitory receptor signaling via PD-1, CTLA-4, NKG2A, TIGIT, LAG-3, CD244 (2B4), and CD160 also mark their exhaustion (Wherry and Kurachi, 2015; Blank et al., 2019). B cell exhaustion is also demonstrated similar to T cell exhaustion with an expression of inhibitory receptors PD-1, CD22, and LAIR-1 but the exhaustion profile of these cells is relatively unexplored (Moir and Fauci, 2014).