Given the mitcochondrial dysfunction obeserved in COVID-19, I have turned my attention towards liver kinase B1 (LKB1). This kinase is intimately involved with both ATP production, T-cell development, peripheral T-cell homeostasis, and T-cell effector function.

I believe SARS-CoV-2 is epigenetically impairing LKB1.  LKB1-deficient T cells exhibited defects in cell proliferation and viability and altered glycolytic and lipid metabolism. Interestingly, loss of LKB1 promoted increased T cell activation and inflammatory cytokine production by both CD4+ and CD8+ T cells.

LKB1 was recently found to have prominent roles in hematopoietic stem cell viability and renewal, suggesting a prominent function for LKB1 in hematopoietic cells. These features are also observed in COVID-19. Inhibition of mTOR induces immunosuppression in transplant rejections and autoimmune disorders. Furthermore, diminished LKB1 reduced t-cell survival and TCR-induced proliferation; increased metabolism and cytokine production.