FcRg, Fc receptor gamma chain; IFNγ, interferon-gamma; NK, natural killer; TNFα, tumor necrosis factor alpha. NK cells in COVID-19–infected people exhibit lower expression of activating receptors including NKp30, NKG2D, NKG2C, CD16, and Fc receptor γ chain (FcRγ) and higher inhibitory NKG2A expression. As a consequence, NK cells exert reduced degranulation and cytokine secretion, which could interactions with other immune cells and contribute to overall hyperimmune activation and tissue injury. Several NK cell–based therapeutics currently in development against COVID-19 infection employ different strategies, including inducing NK cell activation, inhibiting NK exhaustion, and eliciting effector functions of NK cells against infected cells for early clearance of viral infected cells, and prevent tissue injury.