The global outbreak of coronavirus-2019 (COVID-19) still claims more lives daily around the world due to the lack of a definitive treatment and the rapid tendency of virus to mutate, which even jeopardizes vaccination efficacy. At the forefront battle against SARS-CoV-2, an effective innate response to the infection has a pivotal role in the initial control and treatment of disease. However, SARS-CoV-2 subtly interrupts the equations of immune responses, disrupting the cytolytic antiviral effects of NK cells, while seriously activating infected macrophages and other immune cells to induce an unleashed “cytokine storm”, a dangerous and uncontrollable inflammatory response causing life-threatening symptoms in patients. Notably, the NK cell exhaustion with ineffective cytolytic function against the sources of exaggerated cytokine release, acts as an Achilles’ heel which exacerbates the severity of COVID-19. Given this, approaches that improve NK cell cytotoxicity may benefit treatment protocols. As a suggestion, adoptive transfer of NK or CAR-NK cells with proper cytotolytic potentials and the lowest capacity of cytokine-release (for example CD56^dim NK cells brightly express activating receptors), to severe COVID-19 patients may provide an effective cure especially in cases suffering from cytokine storms. More intriguingly, the ongoing evidence for persistent clonal expansion of NK memory cells characterized by an activating phenotype in response to viral infections, can benefit the future studies on vaccine development and adoptive NK cell therapy in COVID-19. Whether vaccinated volunteers or recovered patients can also be considered as suitable candidates for cell donation could be the subject of future research.

2019 年冠状病毒 (COVID-19) 的全球爆发由于缺乏明确的治疗方法和病毒变异的快速趋势，每天仍在世界各地夺去更多生命，这甚至危及疫苗接种的有效性。在与 SARS-CoV-2 的最前沿战斗中，对感染的有效先天反应在疾病的初始控制和治疗中具有关键作用。然而，SARS-CoV-2 巧妙地打断了免疫反应的方程式，破坏了 NK 细胞的细胞溶解抗病毒作用，同时严重激活了受感染的巨噬细胞和其他免疫细胞，引发了一场释放的“细胞因子风暴”，这是一种危险且无法控制的炎症反应，会导致生命- 患者的威胁症状。值得注意的是，NK 细胞衰竭和对细胞因子释放过度的来源无效的细胞溶解功能，充当致命弱点，加剧了 COVID-19 的严重性。鉴于此，改善 NK 细胞细胞毒性的方法可能有益于治疗方案。作为建议，过继转移具有适当细胞溶解潜力和最低细胞因子释放能力的 NK 或 CAR-NK 细胞（例如 CD56^昏暗的 NK 细胞明亮地表达激活受体），对严重的 COVID-19 患者可能提供有效的治疗方法，尤其是在患有细胞因子风暴的情况下。更有趣的是，NK 记忆细胞持续克隆扩增的持续证据表明，NK 记忆细胞以响应病毒感染的激活表型为特征，这可能有利于未来对 COVID-19 疫苗开发和过继性 NK 细胞疗法的研究。接种疫苗的志愿者或康复患者是否也可以被视为细胞捐赠的合适人选可能是未来研究的主题。