Exploring the Utility of NK Cells in COVID-19.
Exploring the Utility of NK Cells in COVID-19.
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DOI：
10.3390/biomedicines10051002
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发表时间：
2022-04-26
期刊：
影响因子：
4.7
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中科院分区：
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2019年冠状病毒病（COVID-19）可表现为急性呼吸窘迫综合征，并与大量发病率和死亡率相关。大量数据表明，对SARS-CoV-2感染的免疫反应决定了COVID-19的病程。已经测试了多种免疫调节剂用于治疗COVID-19。自然杀伤（NK）细胞在抗病毒先天免疫中发挥重要作用，抗SARS-CoV-2活性和抗纤维化活性对于COVID-19控制尤为关键。值得注意的是，SARS-CoV-2清除率、抗体应答和COVID-19的疾病进展与NK细胞状态相关，NK细胞功能障碍与SARS-CoV-2易感性增加有关。因此，NK细胞是COVID-19中从有效免疫反应转变为有害免疫反应的关键因素。然而，在COVID-19患者中观察到NK细胞的失调，表现出与COVID-19严重程度相关的耗竭和功能障碍;这种失调可能有助于疾病进展。鉴于这些发现，具有抗SARS-CoV-2活性、抗纤维化活性和对癌症的强安全性特征的基于NK细胞的疗法可能鼓励功能性NK细胞作为潜在的治疗策略的快速应用，以在早期阶段消除SARS-CoV-2感染的细胞，促进免疫-免疫细胞相互作用，并促进炎症过程，从而预防和/或逆转过度炎症并抑制纤维化进展，从而帮助抗击COVID-19。然而，我们对NK细胞在COVID-19中的作用的理解仍然不完整，需要进一步研究NK细胞在COVID-19发病机制中的参与。基于NK细胞的COVID-19疗法的基本原理必须基于治疗干预的时机和疾病的严重程度，这可能由有益的抗病毒作用和潜在的有害病理作用之间的平衡决定。NK细胞在SARS-CoV-2感染的早期更有效，并可预防COVID-19的进展。NK细胞对调节功能的免疫调节可用作预防COVID-19进展的辅助疗法。
Coronavirus disease 2019 (COVID-19) can manifest as acute respiratory distress syndrome and is associated with substantial morbidity and mortality. Extensive data now indicate that immune responses to SARS-CoV-2 infection determine the COVID-19 disease course. A wide range of immunomodulatory agents have been tested for the treatment of COVID-19. Natural killer (NK) cells play an important role in antiviral innate immunity, and anti-SARS-CoV-2 activity and antifibrotic activity are particularly critical for COVID-19 control. Notably, SARS-CoV-2 clearance rate, antibody response, and disease progression in COVID-19 correlate with NK cell status, and NK cell dysfunction is linked with increased SARS-CoV-2 susceptibility. Thus, NK cells function as the key element in the switch from effective to harmful immune responses in COVID-19. However, dysregulation of NK cells has been observed in COVID-19 patients, exhibiting depletion and dysfunction, which correlate with COVID-19 severity; this dysregulation perhaps contributes to disease progression. Given these findings, NK-cell-based therapies with anti-SARS-CoV-2 activity, antifibrotic activity, and strong safety profiles for cancers may encourage the rapid application of functional NK cells as a potential therapeutic strategy to eliminate SARS-CoV-2-infected cells at an early stage, facilitate immune–immune cell interactions, and favor inflammatory processes that prevent and/or reverse over-inflammation and inhibit fibrosis progression, thereby helping in the fight against COVID-19. However, our understanding of the role of NK cells in COVID-19 remains incomplete, and further research on the involvement of NK cells in the pathogenesis of COVID-19 is needed. The rationale of NK-cell-based therapies for COVID-19 has to be based on the timing of therapeutic interventions and disease severity, which may be determined by the balance between beneficial antiviral and potential detrimental pathologic actions. NK cells would be more effective early in SARS-CoV-2 infection and prevent the progression of COVID-19. Immunomodulation by NK cells towards regulatory functions could be useful as an adjunct therapy to prevent the progression of COVID-19.