Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
Iran University of Medical Science, Tehran, Iran.
Hum Immunol. 2022 Jan;83(1):86-98. doi: 10.1016/j.humimm.2021.09.004. Epub 2021 Sep 8.
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 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.
由于缺乏明确的治疗方法和病毒快速变异的趋势,导致全球 2019 年冠状病毒病(COVID-19)的爆发仍在每天夺走世界各地更多的生命,甚至危及疫苗的疗效。在与 SARS-CoV-2 的前沿战斗中,对感染的有效先天反应在疾病的初始控制和治疗中起着关键作用。然而,SARS-CoV-2 巧妙地打断了免疫反应的平衡,破坏了 NK 细胞的溶细胞抗病毒作用,同时严重激活了受感染的巨噬细胞和其他免疫细胞,导致不受控制的“细胞因子风暴”,这是一种危险的、不可控的炎症反应,会导致患者出现危及生命的症状。值得注意的是,NK 细胞衰竭,对过度释放细胞因子的来源没有有效的溶细胞功能,是 COVID-19 严重程度恶化的阿喀琉斯之踵。鉴于此,提高 NK 细胞细胞毒性的方法可能有助于治疗方案。作为一种建议,向重症 COVID-19 患者输注具有适当细胞毒性潜力和最低细胞因子释放能力(例如 CD56+NK 细胞强烈表达激活受体)的 NK 或 CAR-NK 细胞,可能为治疗提供有效方法,尤其是在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证据表明,它们对病毒感染具有激活表型,可以为 COVID-19 的疫苗开发和 NK 细胞过继治疗的未来研究提供依据。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候选者,可能是未来研究的主题。
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