The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the pandemic of coronavirus disease (COVID-19). Whereas in most cases COVID-19 is asymptomatic or pauci-symptomatic, extremely severe clinical forms are observed. In this case, complex immune dysregulations and an excessive inflammatory response are reported and are the main cause of morbidity and mortality. Natural killer cells are key players in the control of viral infection, and their activity is regulated by a tight balance between activating and inhibitory receptors; an alteration of NK activity was suggested to be associated with the development of severe forms of COVID-19. In this study, we analyzed peripheral NK cell subpopulations and the expression of activating and inhibitory receptors in 30 patients suffering from neurological conditions who recovered from mild, moderate, or severe SARS-CoV-2 infection, comparing the results to those of 10 SARS-CoV-2-uninfected patients. Results showed that an expansion of NK subset with lower cytolytic activity and an augmented expression of the 2DL1 inhibitory receptor, particularly when in association with the C2 ligand (KIR2DL1-C2), characterized the immunological scenario of severe COVID-19 infection. An increase of NK expressing the ILT2 inhibitory receptor was instead seen in patients recovering from mild or moderate infection compared to controls. Results herein suggest that the KIR2DL1-C2 NK inhibitory complex is a risk factor toward the development of severe form of COVID-19. Our results confirm that a complex alteration of NK activity is present in COVID-19 infection and offer a molecular explanation for this observation.

严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 是导致冠状病毒病 (COVID-19) 大流行的原因。尽管在大多数情况下 COVID-19 是无症状或无症状的，但观察到了极其严重的临床形式。在这种情况下，报告了复杂的免疫失调和过度的炎症反应，是发病和死亡的主要原因。自然杀伤细胞是控制病毒感染的关键细胞，它们的活性受激活受体和抑制受体之间的紧密平衡调节；有人认为 NK 活性的改变与严重形式的 COVID-19 的发展有关。在这项研究中，我们分析了 30 名从轻度、中度或重度 SARS-CoV-2 感染中恢复的神经系统疾病患者的外周 NK 细胞亚群以及激活和抑制受体的表达，并将结果与​​ 10 名 SARS-CoV-2-的结果进行了比较。未感染的患者。结果表明，具有较低细胞溶解活性和增强 2DL1 抑制受体表达的 NK 亚群的扩增，特别是与 C2 配体 (KIR2DL1-C2) 结合时，是严重 COVID-19 感染的免疫学情景的特征。与对照组相比，在从轻度或中度感染中恢复的患者中发现表达 ILT2 抑制性受体的 NK 增加。本文的结果表明，KIR2DL1-C2 NK 抑制复合物是导致严重形式的 COVID-19 发展的风险因素。